On Dec. 20, 2006 the United Nations General Assembly passed a landmark resolution recognizing diabetes as a global pandemic. This is a first for a non-infectious disease. This resolution led by the International Diabetes Federation has brought global attention to a disease that affects 246 million people living with diabetes. On Nov. 14, 2007 the UN will observe the First World Diabetes Day.
The financial burden of diabetes is tremendous. The direct and indirect costs associated with both forms of diabetes, type 1 and type 2, in the United States during 2002 were estimated to be $132 billion. The average annual health care costs for a person with diabetes are $13,243, which is 2.4 times greater than those for an individual without diabetes. In 2002, 11 percent of national health care expenditures were directed to diabetes care. The costs of treating the complications of diabetes, which both forms of the disease share in common, account for much of the health care costs associated with the disease. Although estimates of the rates of diabetes have increased since 2002, the associated cost estimates have not yet been revised; hence, the economic data given here are conservative. Clearly, the economic and societal burden of diabetes has a profound impact on the Nation.
Type 1 diabetes is an autoimmune disease in which the body's own immune system attacks and destroys specialized cells of the pancreas called beta cells. Beta cells are found within tiny clusters called islets and produce the hormone insulin. Insulin is required for survival; it sends signals to the body's cells and tissues, telling them to absorb glucose to use as a fuel. Without this vital hormone, the cells and tissues do not absorb glucose and patients can starve to death, despite having high levels of glucose in their bloodstream. An interplay of genetic and environmental factors is responsible for the onset of type 1 diabetes (as well as type 2 diabetes). Having a family member with the disease puts one at higher risk for developing type 1 diabetes.
Type 1 diabetes differs from type 2 diabetes—type 2 is more commonly diagnosed in adulthood, is strongly associated with overweight and obesity and disproportionately affects minority populations. Although patients with type 1 diabetes require externally administered insulin to survive, type 2 diabetes patients may be treated with medications that make their tissues more sensitive to insulin or enhance insulin production or, in some cases, may be treated with insulin itself.
The treatment of patients with type 1 diabetes was revolutionized in 1921 with the discovery of insulin by a group of researchers at the University of Toronto. To this day, insulin therapy continues to save the lives of patients with type 1 diabetes by replacing the essential hormone what their bodies no longer adequately produce. However, insulin therapy, whether through injections or via a pump, is not a cure and it cannot prevent complications. To manage the disease, patients must carefully monitor their food intake and physical activity. They must perform painful finger sticks multiple times a day to draw blood and test their glucose levels. Based on this monitoring, patients often give themselves several shots of insulin a day, or calculate the correct amount of insulin to administer through their insulin pumps. This regimen is not just “once in a while;” it is every day of their lives. As many patients and their parents say; “There is never a day off from diabetes”. Moreover, no matter how vigilant patients are at regulating their blood glucose levels, they can never achieve the fine tuned regulation provided by a healthy pancreas, which exquisitely senses and responds to insulin needs with precise timing.
In 1980 the development of the first animal model of type 1 diabetes that could be used to test drugs for type 1 diabetes; non-obese diabetic (NOD) mouse. Using these NOD mice, doctors from Toronto, the birthplace of insulin discovery, made a revolutionary discovery.
On Dec. 15, 2006, in Canada, a publication in Canada.com reported a Toronto scientist actually appeared to have cured diabetic mice by manipulating the nerves surrounding the insulin-producing islets. Dr. Dosch as early as 1999 concluded that there were surprising similarities between diabetes and multiple sclerosis a central nervous system disease. He suspected a link between the nerves and diabetes. In the article, Dr. Dosch and Dr. Salter used capsaicin, the active ingredient in hot peppers, to kill the pancreatic sensory nerves in mice that had the equivalent of Type 1 diabetes. Once the nerves were deactivated, the islets began producing insulin normally. They had discovered the nerves secrete neuropeptides that are instrumental in the proper functioning of the islets. The University of Calgary and the Jackson Laboratory in Maine found the nerves in diabetic mice were releasing too little of the neuropeptides, resulting in a “vicious cycle” of stress on the islets. In a trial they injected neuropeptide “substance P” in the pancreas of diabetic mice. The islet inflammation cleared up and the diabetes was gone with just one injection. In this study they also discovered that their treatments curbed the insulin resistance that is the hallmark of Type 2 diabetes, and that the insulin resistance is a major factor in Type 1 diabetes, suggesting the two illnesses are quite similar. This research has yet to be tested in clinical trials on humans, but if confirmed it may lead to an irradication of both Type 1 and 2 diabetes.
Solutions to the problem of diabetic disease often involve the use of medications. the most promising appear to be those that can enhance the natural body system called the incretin system, which helps regulate glucose by affecting the beta cells and alpha cells in the pancreas. These prescription medications called dipeptidyl peptidase-4 (DPP-4) inhibitors improve blood sugar control in patients with type 2 diabetes. Through DPP-4 inhibition this new class of drug works when the blood sugar is elevated due to beta-cell dysfunction and uncontrolled production of glucose by the liver due to alpha cell and beta cell dysfunction.
Preferably, these new classes of medications and treatments for diabetes can be more effective when initiated or alternatively combined with the novel use of acoustic shock wave treatments. It is therefore an object of the present invention to treat the pancreas or liver of diabetic diagnosed patients or at risk patients with a tissue regenerating shock wave treatment.
It is also an object of the present invention to provide a shock wave therapy that employs a more effective wave energy transmission, that is both simple to deploy and less target sensitive when compared to reflected focused waves.
It is a further object of the invention to provide a therapeutic treatment of a large target area for subsurface soft tissues of organs such as the pancreas or liver to treat diseases including, but not limited to diabetes.
C. J. Wang discovered that a variety of substances displaying high biological activity are released during and after the application of shock waves to tissue. The production of nitric oxygen (NO), vessel endothelial growth factor (VEGF), bone morphogenetic protein (BMP), and other growth factors have been demonstrated. Furthermore, Maier discovered a decline in the number of small-myelinized neurons after shock wave therapy, an observation that could explain the analgesic effect of shock wave therapy. As a consequence of these findings, the mechanistic model was increasingly relegated to a secondary role and supplanted by a microbiological model explaining the action of shock waves.
In practice the use of ESWT has been a results oriented science wherein a clear and accurate understanding of the actual healing process was neither understood nor fully appreciated. As a result a variety of treatments and uses of ESWT in mammals had heretofore never been tried or attempted or if tried, the outcomes were at best mixed.
A primary factor in the reluctance to use ESWT was that the believed threshold energy requirements were so high that the surrounding tissue would hemorrhage, exhibited by hematomas and bleeding around the treated site. This phenomenon is particularly known in the area of focused emitted waves designed for deep penetration into the patient. US patent publication 2005/0010140 recites the disadvantageous effects of cavitation phenomena can be controlled wherein the shock wave source is connected to a control means which controls the release frequency of shock waves as a function of pulse energy in such a manner that higher pulse energy correlates with lower release frequencies of the shock waves and vice versa. The avoidance of cavitation occurrences would it is postulated result in far less pain for the patient.
In US 2006/0246044 published on Nov. 2, 2006, Andreas Lutz of Dornier Med Tech Systems in Germany disclosed “Methods for Improving Cell Therapy and Tissue Regeneration in Patients With Cardiovascular Disease by Means of Shockwaves”. In this application the use of shock waves is used in combination with cell therapy to assist in heart or neurological tissue regeneration.
The present invention recognizes the underlying beneficial attributes of ESWT are not now and may never be fully comprehended, however, under a more advanced molecular theory the authors of the present invention postulated a microbiological model suggesting the response mechanism to such treatment.
This model attempts to explain the effect of ESWT by postulating neovascularization of the treated tissue with simultaneous release of diverse growth factors. The enhanced metabolic activity taking place in the presence of these growth factors could be responsible for the healing of the chronically inflamed tissue while the decrease in afferent nerve fibers causes the analgesic effect.
The present inventors see that ESWT is a highly versatile therapeutic instrument. It can be used as a bioengineering tool to achieve effects such as the production of growth factors or as a surgical instrument to effect an extremely subtle type of denervation. In the field of traumatology, these properties are used primarily to treat fractures with non-union or delayed osseous union. ESWT is also becoming increasingly important for treating the early stages of osteochondritis dissecans. Heretofore the use of ESWT has never been used as a therapeutic instrument in the treatment of diabetes.
These and other applications of the present invention are described more fully as follows with first detailed description of shock wave therapeutic methods and then a detailed description of several shock wave devices and apparati for carrying out the methods.